Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent

Lysis of autologous human melanoma cells by in vitro allosensitized peripheral blood lymphocytes

Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5-20 different donors. After 6-7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity

Rapid and complete hemopoietic reconstitution following combined transplantation of autologous blood and bone marrow cells. A changing role for high dose chemo-radiotherapy?

The role of high dose chemo-radiotherapy with autologous bone marrow transplantation in the treatment of neoplasia remains to be clearly defined. Because of the iatrogenic morbidity, mortality and high cost of the supportive care required during the post-transplantation period of prolonged marrow aplasia, intensive therapy remains a sophisticated procedure lacking proper evaluation in clinical trials. We report here that when autologous bone marrow cells are supplemented with a small number of peripheral blood nucleated cells collected after prior myelosuppressive chemotherapy, complete hematological recovery is so prompt that myeloid toxicity appears no longer the major limiting factor of high-dose chemo-radiotherapy. The increased therapeutic index made possible by the procedure will allow us to address the issue of whether intensive cytoreductive therapy can be useful as initial treatment of selected tumors with curative intent

Quantitation and typing of hepatitis C Virus RNA in patients on interferon and ribavirin prophylaxis after liver transplantation

HCV can be a major source of graft hepatitis after liver transplantation (OLT) in HCV RNA positive OLT candidates. HCV genotypes were identified in 36 OLT recipients (1b subtype in 30 patients). Recipients were divided in 2 groups whether or not they received post-OLT prophylaxis against HCV graft hepatitis recurrence. Prophylaxis (P) started at the 4th week after OLT in 9 patients (alpha IFN 3 MU/3 times week i.m. + ribavirin 800 mg/day p.o.) while 27 patients were not prophylaxed (NP). Overall 2-year-patient survival was 80% in NP and 100% in P. IFN + ribavirin prophylaxis appears to be effective in controlling HCV graft hepatitis occurrence in the first 6 months after OLT with disappearance of HCV RNA in 3 of 9 patients, irrespective of pretreatment serum HCV RNA levels

Clinical application of growth factors for collection of circulating hematopoietic progenitors in breast cancer patients treated with high-dose cyclophosphamide

Seventy-seven (68 operable breast cancer with > 9 metastatic axillary nodes and 9 inflammatory breast cancer) entered this study. During hematopoietic recovery after cancer therapy with high-dose cyclophosphamide (7 g/m2; HD-CTX) circulating hematopoietic progenitors were collected by leukapheresis (LK) in all patients and then cryopreserved for autologous transplantation. Following HD-CTX, 70 patients were treated with hematopoietic growth factor(s) for 14 days: 38 with rhGM-CSF (group a), 16 with rhIL-3 (group b), 11 with sequential rhIL-3 and rhGM-CSF (group c), 5 with sequential rhIL-3 and rhG-CSF (group d). Seven control patients (group e) did not receive any growth factor. Leukaphereses, carried out over 2-4 consecutive days per patient, were started earlier in group c and in group d patients (mean day: +12 after HD-CTX). The sequential administration of rhIL-3 and rhG-CSF (group d) resulted in clearly higher yield of CFU-GM and CD34+ cells per leukapheresis (65.9 x 10(4)/Kg versus 20.9 x 10(6)/Kg, respectively) if compared with other groups of treatment

Methodologies to estimate circulating hematopoietic progenitors for autologous transplantation in cancer patients

Optimal criteria for harvesting circulating hematopoietic progenitors (CHP) for autologous transplantation to support myeloablative cancer therapy are still uncertain mostly because the CFU-GM assay, the commonly used indirect indicator of the hematopoietic recovery of the graft, is poorly standardized and provides information evaluable only retrospectively. Based on the knowledge that CHP express CD34 and CD33 differentiation antigens and facilitated by the availability of a very efficient fluorescein-conjugated CD34 antibody (8G12), we developed a direct immunofluorescence flow cytometry assay with the aim of replacing the CFU-GM assay advantageously. Recently, in a comparative study, both assays were applied to 157 blood samples obtained daily throughout 20 different recoveries from pancytopenia induced by high-dose cyclophosphamide (7 g/m2) cancer therapy w/ or w/o rhGM-CSF. Results showed that: a) detectability of CD34+ CHP indicated an increase to greater than 500 CFU-GM/mL, a level clinically adequate for harvesting CHP; b) CD34+ cells correlated well with CFU-GM (R=0.89) and data fitted a linear regression line (y=388.3 + 64.0x; y=CFU-GM/mL and x=CD34+/uL); c) in a series of 8 patients treated with myeloablative chemoradiotherapy, early recovery of marrow functions was predicted more accurately by the number of transplanted blood CD34+/CD33+ cells than by nucleated cells, CFU-GM, CD34+/CD33-cells, or CD34-/CD33+ cells. As a guideline, provided platelets are greater than 70,000/uL, harvest of CHP by leukapheresis during recovery from chemotherapy induced pancytopenia should be started as soon as CD34+ cells appear in the circulation and continued until the threshold dose of 7.8x10(6) CD34+ cells/kg, equivalent to 50 x 10(4) CFU-GM/kg, is achieved.(ABSTRACT TRUNCATED AT 250 WORDS

GENOTIPI DELL'HCV IN PAZIENTI SOTTOPOSTI A TRAPIANTO DI FEGATO PER EPATOCARCINOMA SU CIRROSI

La frequenza di evidenza clinica di reinfezione da HCV in pazienti anti-HCV positivi sottoposti a trapianto di fegato(OLTx) per cirrosi \ue8 circa 50%, e in pazienti portatori di epatocarcinoma (HCC) su cirrosi \ue8 >70%; si pu\uf2 ipotizzare per questi ultimi un'infezione primaria con varianti HCV ad alta efficienza di replicazione. Sono stati esaminati 23 pazienti portatori di piccolo HCC su cirrosi sottoposti a OLTx tra 4/91 e 2/94. Tutti i pazienti erano immunosoppressi con ciclosporina A. L'HCV RNA \ue8 stato ricercato nei sieri pre- e post-OLTx con PCR con primers 5'UTR; i genotipi la, lb, 2 e 3 sono stati identificati con primers genotipospecifici del core dell'HCV. Per tutti i casi \ue8 stata determinata la Sierologia per il CMV e la sua diffusione sistemica tramite isolamento in coltura cellulare, viremia p72 e antigenemia pp65. Tutti i pazienti anti-HCV positivi erano HCV RNA positivi pre-OLTx e sono risultati persistentemente HCV RNA positivi durante il follow up. Dei 23 pazienti esaminati pre-OLTx 18 (78%) erano di sottotipo lb, 3 di tipo 2, 1 di sottotipo 1a e 1 di tipo 3. Tutti hanno mantenuto il genotipo pre OLTx durante un follow up mediano di 14 mesi. La distribuzione degli eventi clinici post-OLTx in rapporto ai genotipi dell'HCV e all'infezione da CMV \ue8 la seguente: HCV picco ALT epatite acuta(Bx) CMV Sottotipo 1a (n=1) 1 1 0 Sottotipo 1b (n=18) 13 12 6 Tipo 2 (n=3) 0 0 1 Tipo 3 (n=1) 0 0 0 Da questi dati risulta una elevata frequenza di infezione con sottotipo 1b nei trapiantati di fegato per HCC su cirrosi ed una stretta correlazione tra HCV sottotipo 1b e insorgenza post-OLTx di epatite acuta

Improved collection of mobilized CD34+ hematopoietic progenitor cells by a novel automated leukapheresis system

For simplification of blood cell transplantation, an automated apheresis system that exploits a dual-stage channel device for mononuclear cell (MNC) collection (AutoPBSC, designed for the COBE Spectra) was studied